Expression of anti-apoptosis genes determines the response of adrenal cancer to apoptosis-inducing chemotherapy.

Abstract

BACKGROUND:

This study tested the hypothesis that response of adrenal cortical carcinoma (ACC) to pro-apoptosis drugs depends on expression of anti-apoptosis genes.

MATERIALS AND METHODS:

Expression of Bcl-2 and Bcl-XL proteins was determined in two human adrenal cancer cell lines, NCI-H-295 and RL-251. Two pro-apoptosis drugs, gossypol (G) and docetaxel (D) were tested in vitro and in vivo in a human ACC/SCID mouse chimera.

RESULTS:

Bcl-XL was strongly expressed in RL-251 but not in H-295 and neither expressed the Bcl-2 protein. G and D induced greater dose-dependent inhibition of cell proliferation in RL-251 than in H-295 cells and completely suppressed growth of tumors with high expression of Bcl-XL (p<0.05) while there was no growth suppression in tumors without Bcl-XL expression.

CONCLUSION:

This study provided proof of concept that expression of Bcl-XL determines response to pro-apoptosis drugs. Profiling adrenal tumors for expression of anti-apoptosis genes may provide clues to their potential response to drugs that induce apoptosis.

• Authors: David E Schteingart, Ricardo Benitez, Carol Bradford, Ajita Narayan, Shaomeng Wang
• Journal: Anticancer research (Anticancer Res) Vol. 30 Issue 12 Pg. 4805-9 (Dec 2010) ISSN: 1791-7530 [Electronic] Greece
• PMID: 21187456 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BCL2L1 protein, human
• Proto-Oncogene Proteins c-bcl-2
• Taxoids
• bcl-X Protein
• Docetaxel
• Gossypol

Topics

• Adrenal Cortex Neoplasms (drug therapy, genetics, metabolism, pathology)
• Animals
• Apoptosis (drug effects, genetics)
• Cell Line, Tumor
• Docetaxel
• Genes, bcl-2
• Gossypol (pharmacology)
• Humans
• Mice
• Mice, SCID
• Proto-Oncogene Proteins c-bcl-2 (biosynthesis, genetics)
• Taxoids (pharmacology)
• bcl-X Protein (biosynthesis, genetics)